1. Field of the Invention
The present invention relates to a method of synthesizing (-)-swainsonine and to unique intermediates used in such synthesis.
2. Description of the Prior Art
Swainsonine is a known compound which is a trihydroxy indolizidine alkaloid. It has been isolated from locoweed (Astragalus lentiginosus and Swainsona canescens). It has also been produced from fungus (Rhizoctonia leguminicola and Metarhizium anisopliae).
the alpha-mannosidase inhibitory and immunoregulative properties of (-)-swainsonine have resulted in significant interest in biosynthetic and pharmacological studies of the compound. See, generally, Hino et al., Journal of Antibiotics Vol. 38, 926 (1985); Kino et al., Journal of Antibiotics, Vol 38, 936 (1985); Humphries et al., Proceedings of the National Academy of Sciences (USA) 83 1752 (1986); Dennis, Cancer Research 46,5131 (1986); Granato et al., Molecular Immunology 24, 849 (1987); White et al., Biochemical and Biophysical Research Communications 150, 615 (1988); and Humphries et al., Cancer Research 48, 1410 (1988).
Swainsonine also has been recognized as having potential for use in chemotherapy with cancer patients.
It has also been known to synthesize (-)-swainsonine. See, generally Fleet et al., Tetrahedron Letters 25, 1853 (1984); Ali et al., Journal of Chemical Society Communications 447 (1984); Carbohydrate , 136, 225 (1985); Suami et al., Carbohydrate , 135, 67 (1985); Yasuda et al., Chemistry Letters 1201 (1984); Adams et al., Journal of Organic Chemistry 50, 420 (1985); Setoi et al., Journal of Organic Chemistry 50, 3948 (1985); and Ikota et al., Chemical and Pharmaceutical Bulletin 35, 2140 (1987).
The known methods of synthesis, however, remain rather expensive and inefficient.
In spite of this prior knowledge, there remains a very real and substantial need for an efficient, reliable method of synthesizing swainsonine.